Talquetamab for Advanced Multiple Myeloma Up for Approval in EU
Janssen's request for antibody therapy's use in Europe similar to that filed in US
Janssen Pharmaceuticals is seeking European Union approval for talquetamab, a subcutaneous (under-the-skin) antibody therapy for hard-to-treat multiple myeloma.
The request, in the form of a marketing authorization application to the European Medicines Agency (EMA), will be reviewed under accelerated assessment, which reduces the expected review period from 210 days (nearly seven months) to 150 days (about five months).
“As we deepen our scientific understanding of multiple myeloma, we are focused on advancing our portfolio of innovative therapies to address this complex disease and the needs of patients,” Peter Lebowitz, MD, PhD, global therapeutic area head of oncology at Janssen Research & Development, said in a company press release.
“Today’s submission in Europe marks another important milestone in our progress and ambition to transform the treatment of multiple myeloma,” Lebowitz added.
Talquetamab targets two proteins to potentially kill malignant cells
The submission comes on the heels of a similar application filed in the U.S. in December.
Talquetamab was granted priority medicines and orphan drug designations by the EMA for multiple myeloma, as well as breakthrough therapy and orphan drug status by the U.S. Food and Drug Administration. These designations are meant to speed the therapy’s clinical development and regulatory review.
In multiple myeloma, plasma cells, a type of antibody-producing white blood cell found in the bone marrow, become cancerous and grow out of control. Only 30% of multiple myeloma patients respond to currently available treatments, including immunomodulatory agents, proteasome inhibitors, and CD38 inhibitors.
Talquetamab is a first-in-class, off-the-shelf (ready-to-use) therapy designed to target both GPRC5Da, a receptor protein highly present on the surface of malignant plasma cells, and CD3, a protein on the surface of cancer-killing immune T-cells.
By acting as a bridge between GPRC5D-positive cells and these T-cells, the therapy is expected to promote the death of malignant plasma cells. Talquetamab currently is being evaluated alone or in combination with other treatments.
Regulatory applications were supported by data from the Phase 1/2 MonumenTAL-1 study that enrolled adults with relapsed or refractory multiple myeloma.
Talquetamab at 2 dosing schedules evaluated in ongoing trial
In the trial’s Phase 1 part (NCT03399799), participants received increasingly higher doses of talquetamab, either by subcutaneous injection or intravenous (into the vein) infusion, to establish a safe dose.
According to published data, two optimal under-the-skin injection doses were identified: 405 micrograms (mcg) per kg administered weekly, and 800 mcg/kg given once every two weeks.
Based on these findings, the study’s ongoing Phase 2 part (NCT04634552) is evaluating the safety and efficacy of talquetamab in up to 320 adults whose multiple myeloma has relapsed or failed to respond to at least three lines of therapy. Recruitment is continuing at sites worldwide.
Findings released to date showed that participants, who had received a median of five prior lines of therapy, achieved an overall response rate of 73%. In particular, 74.1% of those receiving the weekly dose and 73.1% of those with twice-monthly dosing saw a reduction in cancer burden after treatment with talquetamab.
In both groups, the median duration of response has been nine months or longer, with longer durations in those achieving a complete response or better.
Reported adverse events were mild or moderate in severity. The most common was cytokine release syndrome, a potentially life-threatening complication marked by fever and multiple organ impairment, experienced by nearly 80% of participants.
Other common side effects included infections, skin- and nail-related disorders, and an altered sense of taste. No treatment-related deaths were reported.
“Despite advances, there remains a high unmet need for those with heavily pretreated multiple myeloma,” said Edmond Chan, MD, senior director, lead of hemato-oncology therapeutic area at Janssen Europe, Middle East & Africa.
“Innovative treatment approaches such as talquetamab, that engage novel cellular targets, are critical for improving outcomes for patients, and we look forward to working with the EMA to bring talquetamab to those in need of new options, as soon as possible,” Chan added.